Proteomics of Primary Hyperoxaluria Type 1

NCT03067142 | Completed

• 2 other identifiers: 64092U54DK083908-06
• Study Type: observational
• Target: 93
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to identify unique urine protein markers of Primary Hyperoxaluria type 1 (PH1) compared to healthy controls. Urine protein markers can be identified by "proteomic" analyses in which proteins are processed in a lab to break them down into smaller building blocks. Using analytical chemistry techniques and specialized equipment many proteins can be identified and measured. Most proteins are found in healthy living cells while subtle changes in these proteins or the presence of different markers reflect abnormal processes and patterns of disease. When identified in disease, protein biomarkers can help to determine if a disease responds to new types of therapies. In this study, changes in urine proteomic patterns over time, their association with change in estimated (calculated) kidney filtering function, and the relative risk for progression of PH1 will be determined. Additionally, as part of the study, the investigators will measure urinary proteins and peptides that are markers of kidney tissue protection (for healthy healing of the kidneys from ongoing damage from high urine oxalate levels, oxalate crystals and stones) to establish if and when these markers are prospectively decreased in PH1 urine. Longitudinal studies of urine "proteomics" may assist in identifying the mechanisms behind PH1-related progression of kidney failure and might contribute important information towards future identification and development of effective therapies to slow or prevent kidney failure in PH1.

Conditions

Primary Hyperoxaluria Type 1

Outcome Measures

Primary Outcomes (1)

• Phase 1: Urine proteomic markers.

  (1) Quantitative Mass Spectrometry analyses will be completed on previously collected, de-identified, and archived urine specimens (collected at only one time point) from patients with Primary Hyperoxaluria type 1 (PH1) and from healthy controls to determine unique protein markers in the urine of PH1 patients, taking into account archived data collected about: (a) known genetic PH1 mutations; (b) concomitant estimated kidney filtering function; (c) urine and plasma oxalate concentrations (using the measure of plasma oxalate when kidney function is low) (d) the level of kidney function (called a "stage"); and (e) any medications and supplements \& their dose and frequency taken for differences in disease (PH1) versus a healthy state. To accomplish this, urine specimens and data which were previously collected, de-identified, and archived will be provided by Mayo Clinic (Rochester, MN) and Ann \& Robert H. Lurie Children's Hospital of Chicago (Chicago, IL).

  Baseline

Secondary Outcomes (2)

• Phase 2: Urine proteomic marker patterns and their change over time related to progression of chronic kidney disease in primary hyperoxaluria type 1 (PH1).

  5 years

• Phase 2: Establish by urine proteome pattern changes if & when normal healing processes of the kidneys are lost, which reflect progressive kidney damage.

  5 years

Study Arms (3)

Cohort 1 (Phase 1): PH1

Cross-Sectional/Observational

Other: Observational

Cohort 2 (Phase 1): Controls

Cross-Sectional/Observational

Other: Observational

Cohort 3 (Phase 2): PH1

Longitudinal/Observational

Other: Observational

Interventions

Observational OTHER

Not an interventional study. Analyses of previously collected urine specimens and data on estimated kidney filtering function.

Cohort 1 (Phase 1): PH1; Cohort 2 (Phase 1): Controls; Cohort 3 (Phase 2): PH1

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Patients with Primary Hyperoxaluria Type 1 (PH1) OR 2. Healthy siblings of those PH1 patients (to serve as "controls)

You may qualify if:

• Have a previously collected 24 hour urine sample from the Mayo Clinic's Rare Kidney Stone Consortium (RKSC) biobank or previously stored at Lurie Children's Hospital (Chicago, IL), a portion of which has been archived (frozen) for future research because you are a patient who has been diagnosed with Primary Hyperoxaluria type 1 (PH1) that is documented by one of the following: (1) PH1 mutation confirmed and/or (2) liver biopsy confirmed; OR
• Have a previously collected 24 hour urine sample, a portion of which has been archived (frozen) for future research, because you are a healthy sibling of a PH1 patient, as described above.

You may not qualify if:

• Have a previously collected 24 hour urine sample because you are a hyperoxaluric patient due to other causes (including secondary hyperoxaluria);
• Have PH1 and have had a 24 hour sample collected but a portion of that specimen has not been archived (frozen) for future research;
• Do not have PH1.

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead
• Mayo Clinic: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Related Publications (9)

• Lapolla A, Seraglia R, Molin L, Williams K, Cosma C, Reitano R, Sechi A, Ragazzi E, Traldi P. Low molecular weight proteins in urines from healthy subjects as well as diabetic, nephropathic and diabetic-nephropathic patients: a MALDI study. J Mass Spectrom. 2009 Mar;44(3):419-25. doi: 10.1002/jms.1520.

  PMID: 19165811 BACKGROUND

• Metzger J, Kirsch T, Schiffer E, Ulger P, Mentes E, Brand K, Weissinger EM, Haubitz M, Mischak H, Herget-Rosenthal S. Urinary excretion of twenty peptides forms an early and accurate diagnostic pattern of acute kidney injury. Kidney Int. 2010 Dec;78(12):1252-62. doi: 10.1038/ki.2010.322. Epub 2010 Sep 8.

  PMID: 20827258 BACKGROUND

• Kistler AD, Serra AL, Siwy J, Poster D, Krauer F, Torres VE, Mrug M, Grantham JJ, Bae KT, Bost JE, Mullen W, Wuthrich RP, Mischak H, Chapman AB. Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study. PLoS One. 2013;8(1):e53016. doi: 10.1371/journal.pone.0053016. Epub 2013 Jan 10.

  PMID: 23326375 BACKGROUND

• Evan AP, Coe FL, Lingeman JE, Shao Y, Sommer AJ, Bledsoe SB, Anderson JC, Worcester EM. Mechanism of formation of human calcium oxalate renal stones on Randall's plaque. Anat Rec (Hoboken). 2007 Oct;290(10):1315-23. doi: 10.1002/ar.20580.

  PMID: 17724713 BACKGROUND

• Yasui T, Fujita K, Hayashi Y, Ueda K, Kon S, Maeda M, Uede T, Kohri K. Quantification of osteopontin in the urine of healthy and stone-forming men. Urol Res. 1999 Aug;27(4):225-30. doi: 10.1007/s002400050114.

  PMID: 10460890 BACKGROUND

• Zhang Y, Wen Z, Washburn MP, Florens L. Refinements to label free proteome quantitation: how to deal with peptides shared by multiple proteins. Anal Chem. 2010 Mar 15;82(6):2272-81. doi: 10.1021/ac9023999.

  PMID: 20166708 BACKGROUND

• Pieper R. Preparation of urine samples for proteomic analysis. Methods Mol Biol. 2008;425:89-99. doi: 10.1007/978-1-60327-210-0_8.

  PMID: 18369889 BACKGROUND

• McIlwain S, Mathews M, Bereman MS, Rubel EW, MacCoss MJ, Noble WS. Estimating relative abundances of proteins from shotgun proteomics data. BMC Bioinformatics. 2012 Nov 19;13:308. doi: 10.1186/1471-2105-13-308.

  PMID: 23164367 BACKGROUND

• Skates SJ, Gillette MA, LaBaer J, Carr SA, Anderson L, Liebler DC, Ransohoff D, Rifai N, Kondratovich M, Tezak Z, Mansfield E, Oberg AL, Wright I, Barnes G, Gail M, Mesri M, Kinsinger CR, Rodriguez H, Boja ES. Statistical design for biospecimen cohort size in proteomics-based biomarker discovery and verification studies. J Proteome Res. 2013 Dec 6;12(12):5383-94. doi: 10.1021/pr400132j. Epub 2013 Oct 28.

  PMID: 24063748 BACKGROUND

MeSH Terms

Conditions

Primary hyperoxaluria type 1

Interventions

Watchful Waiting

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Craig B Langman, MD

  Ann & Robert H Lurie hildren's Hospital of Chicago, Division of Kidney Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: March 1, 2017
• Study Start: January 5, 2017
• Primary Completion: March 30, 2019
• Study Completion: May 31, 2019
• Last Updated: June 12, 2019

Record last verified: 2019-06